This invention is co-pending with U.S. patent application Ser. No. 039,342, which disclosure is incorporated by reference herein.
The invention relates to new optically active hydantoins of the formula I: ##STR2##
Hydrantoins of the formula I are useful starting substances for the stereospecific synthesis of D-(+)-biotin.
Processes for the stereospecific synthesis of D-(+)-biotin from sugars of suitable configuration are known. Thus, D-mannose is used as the starting material in Tetrahedron Letters No. 32, pages 2765-2766 (1975), D-glucose is used in Agric. Biol. Chem. No. 42, page 465 (1978), and D-arabinose is used as the chiral starting material in German Offenlegungsschrift 3,122,562 and German Offenlegungsschrift 3,320,140.
All these processes are characterized, however, by a high number of synthesis steps with consequently a low overall yield. The intermediate stages, which usually cannot be crystallized because of their sugar nature, are frequently obtained only in unsatisfactory purity and, because of their polyfunctionality and the associated chemical instability, require that comparatively narrow reaction parameters be observed. A number of sugars are also not accessible from natural sources, which results in a high cost.
Although the use of L-cysteine, such as is known from U.S. Pat. No. 4,009,172, U.S. Pat. No. 4,130,713 and U.S. Pat. No. 4,337,345 and Journal of the Americal Chemical Society No. 99, page 7020 (1977), avoids handling unstable intermediate stages, it gives only an unsatisfactory yield of optically active D-(+)-biotin via a total of 18 reaction stages, undesirable isomers being removed.
Substituted 3H,5H-imidazo[1,5-c]tetrahydrothiazoles, from which optically active biotin is obtained after racemate resolution, are described in another process in Journal of the Americal Chemical Society No. 105, page 5946 (1983) and in European Offenlegungschrift 0,094,776.
Since the comparatively high number of stages, together with in some cases moderate yields and the need for optical resolution, also makes these starting substances appear to be of little use in the preparation of D-(+)-biotin, there continued to be a demand for suitable starting substances for simple, econimic and stereospecific preparation of D-(+)-biotin.